Cftr Channel Gating : Incremental Progress in Irreversible Steps

Two papers, one in this issue (Weinreich et al. 1999) and the other in the April issue of The Journal (Zeltwanger et al. 1999), help clarify the gating mechanisms of cystic fibrosis transmembrane conductance regulator (CFTR) Cl⁻ channels, the products of the gene found mutated in cystic fibrosis patients. CFTR is a most unusual ion channel. It is a prominent member of the ABC transporter superfamily and comprises two homologous halves, each with a probably hexa-helical transmembrane domain followed, in the primary sequence, by a cytoplasmic nucleotide-binding domain (NBD); the two halves are linked by an ∼20-kD intracellular regulatory (R) domain loaded with sites that can be phosphorylated by PKA and/or PKC (Riordan et al. 1989). Initially dubbed “regulator” because of its transporter family relatives, and more recently fingered as a bona...